Stroke is the third most frequent cause of death in this country, and focal central nervous system (CNS) ischemia is the most common type of stroke. At present there are no generally accepted specific treatments for ischemic strokes. During the previous period of support we developed a method for detailed exploration of biochemical, histological and pharmacological aspects of focal CNS ischemia using a rabbit spinal cord ischemia model. With this technique we found that several inhibitors of serotonin can reduce the amount of neurological damage produced by ischemia. In the proposed studies we will investigate three areas: 1) examination of how serotonin inhibitors reduce CNS ischemic damage; 2) determination of whether several other types of drugs including norepinephrine inhibitors, calcium channel blockers and prostaglandin inhibitors can also reduce CNS injury; 3) exploration of how alterations of arterial blood pressure affect CNS ischemia. To perform these studies we will use the rabbit spinal cord ischemia model to test whether these experimental manipulations affect CNS ischemic damage. We will also measure biogenic amines in many parts of the spinal cord and determine regional spinal cord blood flow to establish the actions of these drugs. Our studies will indicate whether these therapeutic strategies are of potential benefit for patients who suffer ischemic strokes, and will help us understand the mechanisms of action of these treatments so we can design even more effective therapies for CNS ischemia.